This Bioengineering Research Partnership is a consortium of 6 laboratories that are building adaptive optics scanning laser ophthalmoscopes (AOSLOs) and applying them to microscopic examination of the living normal and diseased retina. The principal investigator is David Williams (University of Rochester) who introduced the first successful adaptive optics instruments to vision science. Other lead investigators include: Steve Burns (Indiana University) an international leader in laser scanning ophthalmoscopy, John Flannery (UC, Berkeley) an expert in retinal degeneration and the development of retinal biomarkers, and Austin Roorda (UC, Berkeley) who designed the first adaptive optics scanning laser ophthalmoscopes, David Arathorn (Montana State University) who brings strong mathematical skills and software development tools for tracking the eye in AOSLOs, and R. Daniel Ferguson (Physical Sciences, Inc.) whose expertise is in the optical engineering of innovative eye tracking systems. During years 1-5 of the previous funding period, the partnership designed and built four AOSLO instruments and two more instruments are under construction. These devices have produced the first images ever of numerous microscopic structures in the living eye including the RPE cell mosaic, single leucocytes flowing in the smallest retinal capillaries, and fluorescently-labelled ganglion cell dendrites, axons and cell bodies. In addition, technical challenges for imaging eyes ranging in size from human to rodent have been overcome. The partnership is now proposing continued funding for years 6-10 to develop new capabilities for these instruments such as a combined hardware and software approach to reduce the effects of eye motion on high resolution retinal imagery. We also will develop a new generation of instruments with special capabilities, such as the ability to image ganglion cells in the living human eye without the use of fluorescent dyes, and the ability to optically record neural responses from specific retinal cells. PUBLIC HEALTH RELEVANCE: This application will develop a technology, adaptive optics scanning laser ophthalmoscopy, for taking extremely sharp pictures of the inside of the living eye, so sharp that individual cells can be seen. This technology will be used to study diseases such as age-related macular degeneration and glaucoma. It may allow the earlier detection of retinal disease, better tracking of disease progression, and the efficacy of therapies for retinal disease.